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VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment [ATAC-Seq]

GSE295121 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 21 samples Submitted 2025/11/09 Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 21 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
21 samples: 21 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartmentProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
The trophectoderm (TE), the outer layer of the blastocyst, is the first lineage specified during mammalian development. It initiates attachment and implantation into the maternal endometrium and gives rise to trophoblasts, the epithelial cells of the placenta that support development in utero. Animal models have identified key signaling pathways, including BMP, WNT, and HIPPO, that regulate extra-embryonic ectoderm development, but species-specific differences in regulatory networks underlying TE specification and placental development emphasize the need for human-specific models.
Read the full summary ↓
We were the first to previously identify Vestigial-like Family Member 1 (VGLL1), a coactivator of the TEAD family of transcription factors, as a human-specific placental marker highly expressed in first trimester trophoblast progenitors. The HIPPO signaling pathway effector TEAD4 in complex with YAP1 regulates initial TE specification by acting on key TE transcription factors (TEtra factors): GATA2, GATA3, TFAP2A, and TFAP2C. Pluripotent stem cells (PSCs) represent a unique resource to study species-specific genetic and epigenetic mechanisms of TE and trophoblast development. Here, we use a PSC model in which BMP4 treatment and WNT inhibition (via IWP2) induce TE-like cells. We examined BMP4-dependent chromatin accessibility during the transition from PSC to TE-like cells in relation to gene expression and WNT activation. We found that BMP4 drives chromatin remodeling toward a trophoblast identity and that mesoderm genes are only transiently expressed with canonical WNT activation. Using this model, we determined that, while VGLL1 expression activation is temporally downstream of the TEtra factors, it is necessary for complete trophoblast differentiation by regulating EGFR expression and reinforcing GATA3 activation through positive feedback. We also found that VGLL1 enhanced canonical WNT signaling by directly regulating WNT receptors and effector genes. Furthermore, we identified KDM6B as a direct target of VGLL1. As a chromatin remodeler, KDM6B removes the repressive H3K27me3 at bivalent promoters, enabling the transcriptional activation of TE markers. These findings establish a mechanistic framework that determine the lineage outcomes at the interplay of three developmentally important signaling pathways, HIPPO, BMP, and WNT, positioning VGLL1 at the center of the genetic and epigenetic mechanisms supporting the maintenance and differentiation of human TE and trophoblast cells, key aspects of early placental development.
Published in
VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment
Calderon RI, Sah N, Huang M et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 41284866 · doi:10.1073/pnas.2508432122
This dataset
Open GSE295121 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE295121_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1253590 and SRA study SRP580155. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41284866) ↗
Study design
21 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 21 sample titles: 21 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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